PMID- 16307312
OWN - NLM
STAT- MEDLINE
DCOM- 20060525
LR  - 20081121
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 12
IP  - 6
DP  - 2005 Dec
TI  - Functional assays of HLA A2-restricted epitope variant of latent membrane protein 
      1 (LMP-1) of Epstein-Barr virus in nasopharyngeal carcinoma of Southern China and 
      Taiwan.
PG  - 925-36
AB  - Human leukocyte antigen (HLA) A2 was consistently associated with increased risk 
      for nasopharyngeal carcinoma (NPC) in Chinese populations. Previously we have 
      reported that an Epstein-Barr virus (EBV) strain carrying an HLA A2-restricted 
      epitope variant of LMP-1 is prevalent in NPC in southern China and Taiwan (Lin et 
      al., J. Gen. Virol. 85: 2023-2034, 2004). The variant has mutation selectively 
      involved one of the two anchor residues in position 2 (125 L-->F) and an 
      additional mutation in position 5 (129 M-->I). Functional assays of the epitope 
      variant were carried out in the present work. The stabilization assay on T2 cells 
      indicated that the variant peptide YFL (YFLEILWRL) prevalent in NPC binds to HLA 
      A2 molecules less efficiently than the prototype peptide YLL (YLLEMLWRL). A 
      dose-dependent binding of the HLA A2 molecules with added peptides was observed. 
      In ex vivo cytotoxic T lymphocyte (CTL) assays with CD8-enriched effectors from 
      A2-positive donors revealed that the YLL-specific CTL was able to lyse 
      EBV-infected B cells expressing HLA A2, whereas the CTL recognition was abrogated 
      with the peptide YFL. Cytokine (IFN-gamma) responses, measured both by 
      intracytoplasmic staining and ELISPOT assays after peptide stimulation, also 
      indicated that the variant epitope peptide failed to give an IFN-gamma response. 
      The IFN-gamma response was almost entirely restricted to those tetramer-positive 
      cells. These results show that EBV isolates from NPC of southern China and Taiwan 
      is dominated by an HLA A2-restricted 'epitope-loss variants' of LMP-1, which 
      would allow the virus to resist immune recognition and may in part contribute to 
      the prevalence of NPC in these populations.
FAU - Lin, Hsiang-Ju
AU  - Lin HJ
AD  - Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Cherng, Jaw-Ming
AU  - Cherng JM
FAU - Hung, Man-Shan
AU  - Hung MS
FAU - Sayion, Yiyang
AU  - Sayion Y
FAU - Lin, Jung-Chung
AU  - Lin JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051124
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (Cytokines)
RN  - 0 (EBV-associated membrane antigen, Epstein-Barr virus)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Viral Matrix Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Carcinoma/*metabolism/*virology
MH  - Cell Line, Tumor
MH  - China
MH  - Cytokines/metabolism
MH  - Cytoplasm/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/chemistry
MH  - Flow Cytometry
MH  - Genetic Variation
MH  - HLA-A2 Antigen/*genetics
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nasopharyngeal Neoplasms/*metabolism/*virology
MH  - Peptides/chemistry
MH  - Protein Binding
MH  - T-Lymphocytes, Cytotoxic/metabolism
MH  - Taiwan
MH  - Temperature
MH  - Time Factors
MH  - Viral Matrix Proteins/*metabolism
EDAT- 2005/11/25 09:00
MHDA- 2006/05/26 09:00
CRDT- 2005/11/25 09:00
PHST- 2005/03/09 00:00 [received]
PHST- 2005/07/26 00:00 [accepted]
PHST- 2005/11/25 09:00 [pubmed]
PHST- 2006/05/26 09:00 [medline]
PHST- 2005/11/25 09:00 [entrez]
AID - 10.1007/s11373-005-9017-y [doi]
PST - ppublish
SO  - J Biomed Sci. 2005 Dec;12(6):925-36. doi: 10.1007/s11373-005-9017-y. Epub 2005 
      Nov 24.